Interleikīna-1 un trombocītu GP IIIa receptora polimorfismu ietekme uz neointīmas veidošanos pēc koronāro artēriju stentēšanas - Separamadhu Merinnage Senaratne, Madhavi Mekalani (Latvijas Universitāte, 2009)
Ieviešot stenta implantaciju, lai izplestu sašaurinato arteriju, paradijas asinsvadu restenozes problema. Lai ari tadas jaunas iejaukšanas ka DES un brahiterapija ieverojami samazinaja šo koeficientu, tomer restenoze joprojam uzskatama par problemu visa pasaule. Saprotot, ka iekaisumam varetu but noteikta ietekme neonintimas veidošana, tika veikts liels petijums, lai izprastu faktorus, kas veicina šo procesu. Nesenie petijumi atklaja noteiktas genetiskas ietekmes uz neointimo veidošanos. Šis petijums tika veikts ar merki rast interleukn 1 un trombocita GP III A, genetiska polimorfisma saikni ar neointimo veidošanos. Merki: Noteikt IL -1B (-511), IL -1B (+3954) un IL -1RN VNTR ietekmi uz restenozi. Noteikt trombocita GP III Ars (-5918) PIA ietekmi uz neointimo proliferaciju. Materiali un metodes: Šaja petijuma kopa tika ieklauti 222 pacienti, no kuriem 167 bija virieši un 55 bija sievietes. Slimibas vestures tika iegutas no pacientiem, kam tika veikta perkutana koronara intervence (PKI) laika perioda no 2000. gada lidz 2005. gadam Paula Stradina Kliniskas universitates slimnicas Latvijas Kardiologijas centra (Latvija, Riga). Šiem pacientiem tika savakti pec - intervences un 6 menešu sekojuma IVUS dati. Genetiska informacija tika sanemta no Latvijas biomedicinisko petijumu un studiju centra IL1B veicinataja geniem IL-1B (- 511), IL-1B (- 3954) un inhibicijas genam IL – 1 RN VNTR, ka ari glikoproteina GP III A receptora genam. Cetri parametri: pedeja zaudejuma diametrs (mm), pedeja zaudejuma platiba (mm2), neointima apjoma raditajs (mm3/ mm) un apjoma zuduma procentuala attieciba (%), kas tika aprekinata pec IVUS datiem, kas tika izmantoti, lai novertetu neointimo veidošanos apstradataja vada segmenta. Rezultati: Nekada butiska sakariba starp iekaisuma veicinata geniem IL – 1Beta (-511) un IL – 1B (3954) un neointimo veidošanos. IL - 1 RN VNTR paradija iespejamo tendenci, kad alels 2 klust par daudz aizsargajošaku genu. Tomer nekada vispareji butiska atškiriba netika atklata. Procentuali apjoma zaudejuma vispareja vertiba P = 0,488, un veicot multiplo salidzinašanu starp genotipiem 11 un 22 atklata nenozimiga P = 0,59, un genotipa 22 salidzinašana ar genotipiem (12 + 11) pie P vertibas 0,415 atklaja, ka iegutie rezultati nav butiski. Tomer nepieciešams atzimet, ka tikai 9 pacientiem tika atklats genotips (22). Bez tam aizmugures genotipi netika ieklauti šaja petijuma. Glikoproteina III Ars (5918) PIA gens paradija vispareju saikni ar restenozi. Aplukojot tikai pedeja zaudejuma diametru, butiska saikne starp diametru un 3 genotipiem sastadija P = 0,014, un pedeja zaudejuma platibai vispareja nozime bija P = 0,009. Neointima apjoma raditajs paradija visparejo nozimi (P = 0,019) un vien aptuvenu nozimi (P = 0,053) starp C/ T pret T/ T. Procentuals apjoma zudums (P = 0,013) atklaja butisku atškiribu starp genotipiem C/ T un T/ T (P = 0,018). Secinajumi: Netika atklata nekada saistiba starp IL - 1Beta veicinataju ražojošiem geniem IL - 1B (– 511) un IL - 1B (-3954) un neointimo veidošanos. Lai ari šaja petijuma tas netika paradits, tomer pastav iespeja, ka IL1 RN VNTR gena * 2 alelam ir daudz aizsargajošaka ietekme uz restenozi. Tika atklata GP III Ars (-5918) PIA gena ietekme uz neointimalo proliferaciju. Tacu nebija iespeju noteikt dominejoši ietekmeto alelu, jo starp šiem diviem aleliem nav linearas korelacijas. Nepieciešams veikt plašus turpmakus petijumus ar daudzejadu neointimas veidošanas salidzinašanu un attieciba uz saikni ar iespejamajiem veicinošajiem genetiskiem un fenotipiskiem faktoriem, lai rastu labaku risinajumu restenozei.

Background: With the introduction of stent implantation to dilate a narrowed artery followed with the nagging problem of restenosis of a blood vessel. Although new interventions such as DES and Brachytherapy have reduced this rate dramatically, restenosis is still a problem world wide. With the understanding that inflammation might be having some effect over the formation of neoinintima much research work is been done to understand the contributory factors for this process. Recent researches have shown some genetic influences on neointimal formation. This study was done to see an association of interleukn 1 and platelet GP III A, genetic polymorphism with neointimal formation. Objectives: To determine IL -1B (-511), IL -1B (+3954) and IL -1RN VNTR effect on restenosis. To determine the effect of platelet GP III Ars (-5918) PIA on the neointimal proliferation Materials and Methods: A total of 222 patients were included in the study out of which 167 were males and 55 were females. Case histories were collected from patients who had undergone Percutaneous coronary intervention (PCI) from 2000 – 2005 at the Latvian Centre of Cardiology at Paula Stradina Clinical University Hospital (Riga, Latvia). For these patients post intervention and 6 months follow up IVUS data was collected. Genetic information was received by the Latvian biomedical Research and study centre for IL1B promoter genes IL-1B (- 511), IL-1B (- 3954) and inhibitory gene IL – 1 RN VNTR and glycoprotein GP III A receptor gene. Four parameters: late loss diameter (mm), late loss area (mm2), neointimal volume index (mm3/mm) and percentage of volume loss (%) which was calculated from IVUS data was used to evaluate neointimal formation in the treated vessel segment.Results: No significant relation between inflammatory promoter genes the genes IL – 1Beta (-511) and IL – 1B (3954) and neointima formation was seen. IL-1 RN VNTR showed a possible tendency of allele 2 been the more protective gene. However no over all significant different was found. On percentage volume loss an overall value of P = 0.488 and when doing multiple comparisons, between the genotypes 11 and 22 a non significance of P = 0.59 and genotype 22 vs. genotypes (12 +11) a P value of 0.415 showed that it there is no significance for the obtained results. However it should be noted that only 9 patients were present for the genotype (22). And the rear genotypes were not included in this study. Glycoprotein III Ars (5918) PIA gene showed an overall association with restenosis. When taking late loss diameter only the significant association between diameter and the 3 genotypes was P = 0.014 and for late loss area the over all significance was P = 0.009. Neointimal volume index showed overall significance (P = 0.019) and only a near significance (P = 0.053) between C/T vs. T/T. Percentage volume loss (P = 0.013) showed a significant difference between the genotypes C/T vs. T/T (P = 0.018). Conclusions: No association between the promoters of IL-1Beta producing genes IL-1B (– 511) and IL- 1B (-3954) and the neointima formation was seen. Although it was not shown by this study there is a possibility for the IL1 RN VNTR gene * 2 allele to have more protective effect on restenosis. An affect of GP III Ars (-5918) PIA gene on noeointimal proliferation is seen. However it is unable to determine the dominantly affected allele since there is no linear correlation between the two alleles. Further studies with multivariate comparisons on neointima formation and association with the possible contributory genetic and phenotypic factors should be done extensively in order to find a better solution for restenosis.
Impact of interleukin1 and platelet GP III A polymorphisms on formation of neo-intima after coronary artery stenting
Keywords: Medicīna